Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000551.4(VHL):c.463+8C>T

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA020379

127830 (ClinVar)

Gene: VHL

Condition: von Hippel-Lindau disease

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: aafdfd2b-5500-4e62-8d25-16de393ad917

Approved on: 2024-06-25

Published on: 2024-06-25

HGVS expressions

NM_000551.4:c.463+8C>T

NM_000551.4(VHL):c.463+8C>T

NC_000003.12:g.10146644C>T

CM000665.2:g.10146644C>T

NC_000003.11:g.10188328C>T

CM000665.1:g.10188328C>T

NC_000003.10:g.10163328C>T

NG_008212.3:g.10010C>T

ENST00000696142.1:c.*140+8C>T

ENST00000696143.1:c.600-3143C>T

ENST00000696153.1:c.463+8C>T

ENST00000256474.3:c.463+8C>T

ENST00000256474.2:c.463+8C>T

ENST00000345392.2:c.341-3143C>T

ENST00000477538.1:n.599+8C>T

NM_000551.3:c.463+8C>T

NM_198156.2:c.341-3143C>T

NM_001354723.1:c.*18-3143C>T

NM_001354723.2:c.*18-3143C>T

NM_198156.3:c.341-3143C>T

Benign

BA1

Evidence Links 1

Expert Panel

VHL VCEP

Criteria Specification Information

Criteria Specification: ClinGen VHL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for VHL Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

VHL VCEP

The variant NM_000551.4(VHL):c.463+8C>T is an intronic variant. The GroupMax Filtering Allele Frequency (95% CI) in gnomAD v4.1.0 is 0.001101 (1359/1179388 from European, Non-Finnish Population). This is higher than the ClinGen VHL VCEP threshold of >=0.000156 (0.0156%) threshold expected for VHL disease (BA1). Therefore this variant meets the criterion for (BA1) and is classified as Benign for autosomal-dominant von Hippel-Lindau disease (VHL disease) based on the ACMG/AMP criteria applied, as specified by the ClinGen VHL VCEP Version 1.0 (Specifications approval date: 02/26/2024. Variant Approval Date 06/25/2024).

BA1

The GroupMax Filtering Allele Frequency (95% CI) in gnomAD v4.1.0 is 0.001101 (1359/1179388 from European, Non-Finnish Population). This is higher than the ClinGen VHL VCEP threshold of >=0.000156 (0.0156%) threshold expected for VHL disease (BA1).

This article details a case with the c.463+8C>T splice variant. The reported case is 63yo with pheochromocytoma but lacking any family history of hereditary cancer syndrome or other VHL tumor/phenotypes. 2 of 3 offspring (not detailed) carry the same variant, the authors do not comment on their phenotypes. The authors speculate in the discussion that this variant is a rare polymorphism. PubMed:9398721

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.